The objectives of this contract is to investigate the toxicity and carcinogenicity of codeine (a widely used drug) in rats and mice. To accomplish these objectives, a 104-week chronic study at 3 dose levels plus controls, including an interim evaluation at 65 weeks will be conducted. Additional animals shall be treated for 1, 30, 90, 180 or 365 days and 4 animals per dose/sex/specie shall be sacrificed at one of five time points on those days for plasma collection. The plasma samples shall be frozen and shipped to a designated laboratory for codeine and/or its metabolite deter- mination.